Clostridium Botulism - WHO

CLOSTRIDIUM
BOTULINUM
International Programme on Chemical Safety
Poisons Information Monograph 858
Bacteria
WORLD HEALTH ORGANIZATION
International Programme on Chemical Safety Poisons Information Monograph 858
Bacteria ______________________________________________________________________________Clostridium Botulinum
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TABLE OF CONTENTS
1. NAME........................................................................................................................................................................ 5
1.1 Scientific name................................................................................................................................................ 5
1.2 Family.............................................................................................................................................................. 5
1.3 Common names and synonyms...................................................................................................................... 5
2. SUMMARY................................................................................................................................................................ 5
2.1 Main risks and target organs........................................................................................................................... 5
2.2 Summary of clinical effects.............................................................................................................................. 5
2.3 Diagnosis........................................................................................................................................................ 6
2.4 First Aid Measures and Management Principles............................................................................................. 7
2.5 Poisonous parts.............................................................................................................................................. 7
2.6 Main Toxins..................................................................................................................................................... 8
3. CHARACTERISTICS............................................................................................................................................... 8
3.1 Description of the bacterium........................................................................................................................... 8
3.1.1 Special identification features................................................................................................................ 8
3.1.2 Habitat ................................................................................................................................................... 8
3.1.3 Distribution............................................................................................................................................. 8
3.2 Poisonous parts.............................................................................................................................................. 9
3.3 The Toxin........................................................................................................................................................ 9
3.3.1 Name(s)................................................................................................................................................. 9
3.3.2 Description, chemical structure, stability................................................................................................ 9
3.3.3 Other physicochemical characteristics................................................................................................. 10
3.4 Other Chemical Contents of the bacteria...................................................................................................... 10
4 USES/CIRCUMSTANCES OF POISONING...................................................................................................... 10
4.1 Uses.............................................................................................................................................................. 10
4.1.1 Uses.................................................................................................................................................... 10
4.1.2 Description........................................................................................................................................... 10
4.2 High risk circumstances................................................................................................................................ 10
4.3 High risk geographical areas......................................................................................................................... 12
5. ROUTES OF EXPOSURE................................................................................................................................. 12
5.1 Oral ............................................................................................................................................................... 12
5.2 Inhalation...................................................................................................................................................... 13
5.3 Dermal........................................................................................................................................................... 13
5.4 Eye................................................................................................................................................................ 13
5.5 Parenteral ..................................................................................................................................................... 13
5.6 Others........................................................................................................................................................... 13
6. KINETICS.......................................................................................................................................................... 14
6.1 Absorption by route of exposure................................................................................................................... 14
6.2 Distribution by routes of exposure................................................................................................................. 14
6.3 Biological half-life by routes of exposure....................................................................................................... 14
6.4 Metabolism.................................................................................................................................................... 14
6.5 Elimination and excretion.............................................................................................................................. 14
7. TOXINOLOGY................................................................................................................................................... 15
7.1 Mode of action............................................................................................................................................... 15
7.2 Toxicity.......................................................................................................................................................... 15
7.2.1 Human data......................................................................................................................................... 15
7.2.2 Relevant animal data........................................................................................................................... 16
7.2.3 Relevant in vitro data........................................................................................................................... 16
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7.3 Carcinogenicity.............................................................................................................................................. 17
7.4 Teratogenicity................................................................................................................................................ 17
7.5 Mutagenicity.................................................................................................................................................. 17
7.6 Interactions.................................................................................................................................................... 17
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS......................................................... 17
8.1 Material sampling plan.................................................................................................................................. 17
8.1.1 Sampling and specimen collection...................................................................................................... 17
8.1.2 Storage of laboratory samples and specimens.................................................................................... 18
8.1.3 Transport of laboratory samples and specimens................................................................................. 18
8.2 Biomedical investigations and their interpretation......................................................................................... 19
8.2.1 Biochemical analysis........................................................................................................................... 19
8.4 Other biomedical (diagnostic) investigations and their interpretation............................................................ 19
9. CLINICAL EFFECTS......................................................................................................................................... 19
9.1 Acute poisoning............................................................................................................................................. 19
9.1.1 Ingestion.............................................................................................................................................. 19
9.1.2 Inhalation............................................................................................................................................. 20
9.1.3 Skin exposure...................................................................................................................................... 20
9.1.4 Eye contact.......................................................................................................................................... 20
9.1.5 Parenteral exposure............................................................................................................................ 20
9.2 Chronic poisoning......................................................................................................................................... 20
9.2.1 Ingestion.............................................................................................................................................. 20
9.2.2 Inhalation............................................................................................................................................. 20
9.2.3 Skin exposure...................................................................................................................................... 20
9.2.4 Eye contact.......................................................................................................................................... 20
9.2.5 Parenteral exposure............................................................................................................................ 21
9.3 Course, prognosis, cause of death............................................................................................................... 21
Foodborne botulism...................................................................................................................................... 21
9.4 Systematic description of clinical effects....................................................................................................... 21
9.4.1 Cardiovascular..................................................................................................................................... 21
9.4.2 Respiratory.......................................................................................................................................... 21
9.4.3 Neurological......................................................................................................................................... 21
9.4.4 Gastrointestinal.................................................................................................................................... 22
9.4.5 Hepatic................................................................................................................................................ 22
9.4.6 Urinary................................................................................................................................................. 22
9.4.7 Endocrine and reproductive systems................................................................................................... 22
9.4.8 Dermatological..................................................................................................................................... 22
9.4.9 Eye, ear, nose, throat: local effects..................................................................................................... 23
9.4.10 Haematological.................................................................................................................................... 23
9.4.11 Immunological ..................................................................................................................................... 23
9.4.12 Metabolic............................................................................................................................................. 23
9.4.13 Allergic reactions................................................................................................................................. 23
9.4.14 Other clinical effects............................................................................................................................ 23
9.4.15 Special risks........................................................................................................................................ 23
9.5 Other............................................................................................................................................................. 24
10. MANAGEMENT................................................................................................................................................. 24
10.1 General principles.................................................................................................................................... 24
10.2 Life supportive procedures and symptomatic/specific treatment.............................................................. 24
10.3 Decontamination...................................................................................................................................... 24
10.4 Enhanced elimination............................................................................................................................... 25
10.5 Antidote/antitoxin treatment...................................................................................................................... 25
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11. ILLUSTRATIVE CASES...................................................................................................................................... 27
11.1 Case reports from literature...................................................................................................................... 27
12. ADDITIONAL INFORMATION........................................................................................................................... 28
12.1 Specific preventive measures................................................................................................................... 28
13. REFERENCES.................................................................................................................................................. 29
14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE ADDRESSES............... 32
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1. NAME
1.1 Scientific name
Clostridium botulinum
1.2 Family
Clostridium
Endospore-forming gram-positive bacilli
1.3 Common names and synonyms
Botulinum toxin;
Toxinum botulinum;
Botulinum A toxin haemagglutinin complex;
Oculinum (Allergan Pharmaceuticals, USA);
Botox (produced by Allergan Pharmaceuticals, USA);
Dysport (produced by Ipsen, UK);
OcL ^CcCc_ [LC_
2. SUMMARY
2.1 Main risks and target organs
Botulism is characterised by symmetrical, descending, flaccid paralysis of motor and autonomic
nerves usually beginning with cranial nerves. It occurs when neuromuscular transmission is inter-
rupted by a protein neurotoxin produced by the spore-forming, obligate anaerobic bacterium Clos-
tridium botulinum. Paralysis begins with the cranial nerves, then affects the upper extremities, the
respiratory muscles, and, finally, the lower extremities in a proximal-to-distal pattern. In severe
cases, extensive respiratory muscle paralysis leads to ventilatory failure and death unless suppor-
tive care is provided.
2.2 Summary of clinical effects
There are five clinical categories of botulism: 1) foodborne botulism; 2) wound botulism; 3) infant
botulism; 4) adult infectious botulism; 5) inadvertent, following botulinum toxin injection.
Foodborne botulism
Onset generally occurs 18 to 36 hours after exposure (range, 6 hours to 8 days). Initial symptoms
can include nausea, vomiting, abdominal cramps or diarrhoea. After the onset of neurologic
symptoms, constipation is typical. Dry mouth, blurred vision, and diplopia are usually the earliest
neurologic symptoms. They are followed by dysphonia, dysarthria, dysphagia, and peripheral
muscle weakness. Symmetric descending paralysis is characteristic of botulism.
Wound botulism
This can be defined as clinical evidence of botulism following lesions, with a resultant infected
wound and no history suggestive of foodborne illness. Except for the gastrointestinal symptoms, the
clinical manifestations are similar to those seen in foodborne botulism. However, the incubation
period is much longer as time is required for the incubation of spores, growth of clostridium and
release of toxins (4 to 14 days).
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Infant botulism
This is caused by the absorption of toxin produced by Clostridium botulinum that colonize the
intestinal tracts of infants under one year of age. It is often associated with ingestion of honey and
the first clinical sign is usually constipation. After a few weeks, progressive weakness and poor
feeding are observed. The weakness is symmetrical and descending. It evolves over hours or
several days. The infant is afebrile and has a weak cry, has either absent or diminished
spontaneous movements, decreased sucking, floppy head and decreased motor response to
stimuli. The autonomic nervous system manifestations include dry mucous membranes, urinary
retention, diminished gastro-intestinal motility, fluctuation of heart rate, and changes in skin colour.
Duration of hospitalisation may last from a few days to six months.
Adult infectious botulism
It occurs as a result of intestinal colonization with C. botulinum and in vivo toxin production in a
manner similar to that of infant botulism. These patients often have a history of abdominal surgery,
achlorhydria, Crohns disease or recent antibiotic treatment. The disease may simulate a Guillain-
Barr Syndrome.
Inadvertent botulism
This has been reported in patients who have been treated with intramuscular injections of botulinum
toxin. Marked clinical weakness is observed as well as electrophysiologic abnormalities.
2.3 Diagnosis
Foodborne botulism
This should be suspected in a patient with acute onset of gastro-intestinal symptoms associated
with autonomic (dry mouth, difficulty focusing eyes) and cranial nerves dysfunction (ptosis, diplopia,
dysarthria, dysphagia). A history of home-prepared or home-preserved food (often, inadequately
pasteurized vegetables) and similar symptoms in people who have shared the same food increases
likelihood of the diagnosis. The initial diagnosis should be made on the basis of history and physical
findings. Confirmatory tests may take days to be performed. Serum, stools and suspected food
should be tested for the presence of botulism. The mouse inoculation test is still the most reliable
method. Stool specimens should be cultured for C. botulinum as a confirmatory test. Isolation of C.
botulinum organism devoid of toxin from the suspected food has little significance.
Wound botulism
Specimens of wound exudate, a tissue sample, or a swab sample should be obtained for anaerobic
culture in addition to a serum toxin assay. A stool specimen should be obtained in order to exclude
food or intestinal colonization as sources of toxin.
Infant botulism
This should be suspected in an infant with constipation, poor feeding, diminished sucking and crying
ability, neck and peripheral muscle weakness, or ventilatory distress. Stool cultures for C. botulinum
and testing for the presence of toxin in the stool should be performed in such patients.
This is a rare disease and should be suspected in patients with some abnormality of the gastro-
intestinal tract who develop cranial nerve autonomic dysfunction, and muscular weakness. Stool
cultures for C. botulinum and testing for the presence of toxin should be performed. Endogenous
antibody production to botulinum toxin has been described.
This may be suspected in patients with recent history of botulin A toxin injection, especially into big
muscles for systemic effect, or perhaps, in a suicide attempt.
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2.4 First Aid Measures and Management Principles
Foodborne botulism
Emptying the stomach by gastric lavage or induction of vomiting with syrup of ipecac could be con-
sidered if the suspected food ingestion was recent (within 1 hour). It should not be attempted if neu-
rological symptoms are already present.
Administer activated charcoal and a cathartic (such as sorbitol) but not magnesium salts since
magnesium may potentiate neuromuscular block. Maintain airway and assist ventilation if required.
Obtain arterial blood gases. Monitor respiration closely since respiratory arrest can occur abruptly.
Administer Trivalent ABE antitoxin (7500 IU of type A, 5500 IU of type B, and 8500 IU of type E
antitoxins) per patient. First test for serum sensitivity by injecting 0.1 mL of a 1:10 dilution of
antitoxin in saline intradermally. Monitor for any reaction for 15 minutes before administering a full
dose. If a reaction occurs the dose and rate of infusion must be reduced and the reaction must be
treated. A single dose of antitoxin is usually sufficient.
Wound botulism
Because of the slow recovery period, trivalent antitoxin administration may need to be repeated.
Infant botulism
Equine botulinum antitoxin is not used in infant botulism because of the potential risk of
anaphylaxis, serum sickness, or the sensitization of the infant to horse antigen. A human-derived
antitoxin product (immune globulin) is being evaluated in a controlled trial in California (USA) for use
in infants. For information on the Infant Botulism Prevention Programme contact the California
Department of Health Services at (510) 540-2646 (24 hours).
Trivalent antitoxin may need to be readministered after the first dose because of the prolonged
evolution.
2.5 Poisonous parts
Botulism is caused by a group of anaerobic spore-forming organisms called Clostridium botulinum.
This is classified as a single species but consists of at least three genetically distinguishable groups
of organisms that have been recognized as toxic for humans. They share the ability to produce
neurotoxins with similar pharmacological activities but diverse serologic properties. The toxin types
are classified as A, B, C, D, E, F and G. Human botulism has been described with the strains of
Clostridium botulinum that produce toxin types A, B and E. Less frequently, cases involving type F
toxin produced by C. baratii and type E toxin produced by C. butyricum have been published
8
2.6 Main Toxins
Although the seven neurotoxins (A, B, C, D, E, F and G) are genetically distinct, they possess
similar molecular weights and have a common subunit structure. The complete amino acid
sequences of the various serotypes are becoming known. Regions of sequence homology among
the serotypes and between botulinum toxins and tetanus toxin, suggest that they all employ similar
mechanisms of action.
The toxins are synthesized as single chain polypeptides with a molecular mass of approximately
150 kDa. In this form, the toxin molecules have relatively little potency as neuromuscular agents.
Neurotoxin activation requires a two-step modification in the tertiary structure of the protein.
3. CHARACTERISTICS
3.1 Description of the bacterium
3.1.1 Special identification features
Clostridium botulinum is a gram positive, obligate anaerobic, spore-forming, rod-shaped
bacterium.
3.1.2 Habitat
Clostridium botulinum organisms are commonly found in soils and marine sediments
throughout the world.
3.1.3 Distribution
C. botulinum may be found in any region of the world. Since it is found in the soil, it may
contaminate vegetables cultivated in or on the soil. It also colonizes the gastro-intestinal
tract of fishes, birds and mammals.
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3.2 Poisonous parts
All clostridial neurotoxins are synthesized as a single inactive polypeptide chain of 150 kDa without
a leader sequence and hence are presumably released from the cell by bacterial lysis (Schiavo et
al, 1995).
The organisms that can produce botulinum neurotoxin are diverse. Even though they were shown to
have different phenotypic characteristics, all organisms capable of producing botulinum neurotoxin
become classified as Clostridium botulinum (Prevot, 1953).
These are the characteristic of clostridia capable of producing botulinum neurotoxin:
C. BOTULINUM GROUP
I II III IV* C. baritii C. butyricum
Toxin type A, B, F B, E, F C, D G F E
Growth temperature (C)
Optimum 35 40 18 25 40 37 30 37 30 45
Minimum 12 3.3 15 10
* C. argentinense has been proposed for this group (Hatheway, 1995).
3.3 The Toxin
3.3.1 Name(s)
Human botulism is primarily caused by Clostridium botulinum that produce toxin type A, B
and E. Type F toxin produced by Clostridium baratii and type E toxin produced by
Clostridium butyricum have also been implicated in human botulism.
Strains of C. botulinum that produce type C or type D toxin for the most part cause
botulism only in non-human species (Shapiro et al, 1998).
3.3.2 Description, chemical structure, stability
All clostridial neurotoxins are synthesized as a single inactive polypeptide chain of
150 kDa without a leader sequence and hence are presumably released from the cell by
bacterial lysis. Bacterial or tissue protease cleaves these toxins within an exposed highly
protease-sensitive loop and generates the active di-chain neurotoxins composed of a
heavy chain (H, 100 kDa) and a light chain (L, 50 kDa) joined by disulphide bonds, that is
associated with one atom of zinc. This interchain S-S bond plays a critical role in cell
penetration, and its cleavage by reduction abolishes toxicity (Schiavo et al, 1995).
The heavy chain can be divided functionally into an amino terminal domain (Hn) and a
carboxyl terminal domain (Hc) (Halpern & Neale, 1995).
The light chain (amino acids 1-448) acts as a zinc endopeptidase, with proteolytic activity
concentrated at the N-terminal end. The heavy chain (amino acids 449-1280) provides
cholinergic specificity and promotes light chain translocation across the endosomal
membrane of the neurotransmitter.
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If the disulphide bond that links the two chains is broken before the toxin is internalised in
the cell, the light chain cannot enter the axon terminal membrane, and there is a virtually
complete loss of toxicity (Brin, 1997) (see 7,1 Mode of action).
3.3.3 Other physicochemical characteristics
The toxin in the complex is rather stable, especially under acidic conditions (pH 3,5 to
6,5), but the complex dissociates under slightly alkaline conditions and the biological
activity is readily inactivated in this state. The neurotoxin can be separated from the non-
toxic components and purified by ion-exchange chromatography (Midura, 1996). Although
botulinum spores are relatively heat resistant the toxin itself is heat sensitive. Heating it at
80C for 30 minutes or 100C for 10 minutes destroys the active toxin (Slovis & Jones,
1998).
3.4 Other Chemical Contents of the bacteria
C. botulinum spores produced by all strains are highly heat resistant. Toxins produced by some
Clostridium botulinum bacteria are non-proteolytic, which means that affected food may look and
smell normal (Cherington, 1998).
4 USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.1.1 Uses
Neurotoxin: Pharmaceutical for human use (agent acting on the nervous system); Other
Bacterium: Warfare/Anti riot agent: biological warfare agent
4.1.2 Description
Botulin toxin A is used in the treatment of spastic muscular conditions such as torticollis,
cervical and upper limb dystonia, childhood strabismus, apraxia of eye-lid opening,
hemifacial spasm, writers cramp, spasticity in cerebral palsy in children, but also in the
treatment of hyperhidrosis (Munchau & Bhatia, 2000). It is also used for cosmetic
purposes to reduce wrinkles.
4.2 High risk circumstances
There are 5 clinical categories of botulism of which the foodborne type is the most common.
Canned or bottled food, particularly homemade, may contain botulinum (Cherington, 1998; Slovis &
Jones, 1998).
Foodborne botulism
Home-prepared and home-preserved foods (often inadequately pasteurized vegetables, despite
the name coming from the Latin botulus =sausage) are the most frequent cause of poisoning. The
particular foods involved vary according to geographical and cultural peculiarities:
Strong-smelling preserved bean curd in China (Ying & Shuyan, 1986)
Canned vegetables in U.S.A (MacDonald et al, 1986)
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Meat from marine animals or fish/fish eggs fermented in traditional ways in Canada (Hauschild &
Gauvreau, 1985)
Preserved ham (Lecour et al, 1988 ; Roblot et al, 1994)
Home-made sauces; baked potatoes sealed in aluminum foil; cheese sauce; sauted onions held
under a layer of butter; garlic in oil; traditionally prepared salted or fermented fish
The vehicles for botulism change with time even in the same country. For example, in USA, new
sources have been described in recent years (Shapiro et al, 1998; Townes et al, 1996). This
influences the type of toxin involved (Hatheway, 1995; Hauschild, 1992). Cases recorded in 38
countries between 1951 and 1989 show that 72 % of the outbreaks and 48 % of the cases were
reported from Poland. Of the 2622 outbreaks in which the toxin type was determined, 34 % were
type A, 52 % type B, and 12 % type E. Two incidents of type F foodborne botulism were reported
during this period.
Wound botulism
A review of 40 cases of wound botulism published in the literature (Mechem & Walter, 1994)
showed that most of these cases involved puncture wounds, open fractures, lacerations, crush
injuries, shotgun wounds, drug abuse (abscesses), and surgical incisions. In some cases, no site of
inoculation could be found. In the 13 cases where the toxin was isolated, 11 had type A, one had
type B and the type of the toxin was not mentioned in one case. The use of Mexican black tar
heroin was responsible for a cluster of cases in California (Anderson et al, 1997; Maselli et al,
1997).
Infant botulism
In most cases, the source of ingestion is unknown but in 15 % of cases, ingestion of honey is
suspected (Shapiro et al, 1998).
The toxin type in infant botulism is generally either A or B, and the organisms are group I C.
botulinum. Two cases have been reported in USA involving strain C. baratii that produce a
neurotoxin similar to type F and two cases have been reported in Italy caused by strains C.
butyricum that produce type E neurotoxin (Hatheway, 1995).
Two patients with clinical signs and symptoms of botulism yielded C. botulinum type A in their stool
cultures for as long as 119 and 130 days after onset of illness (Hatheway, 1995).
Factors associated with this form of botulism were bowel surgery, Crohn's disease, or previous
contaminated food exposure without illness.
This is a more recent form of botulism caused by the use of the toxin to treat dystonic and other
movement disorders (Cherington, 1998; Bhatia et al 1999). In patients with torticollis treated with
botulinum A toxin injected into the neck muscles dysphagia may develop from toxin penetrating the
nearby pharyngeal muscles. The penetration of the toxin to distant muscles or generalized
weakness due to systemic distribution of the toxin is rare (Bakheit et al, 1997; Bhatia et al, 1999).
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4.3 High risk geographical areas
Out of 449 outbreaks with 930 cases reported in literature reviews (Hatheway, 1995), 72 % of the
outbreaks and 48 % of the cases occurred in Poland.
Clostridial spores are resistant to heat and may survive the home-preserving process at
temperatures below 120 C. At high altitude boiling food prior to canning may not provide a high
enough temperature to destroy the spores (Cherington, 1998).
Traditional food preparation and preservation is a major factor in the production of foodborne
botulism (Hauschild, 1992). Non-acidic foods need to be pasteurized twice, at 24h intervals, to kill
the bacteria generated from the surviving spores (Cherington, 1998).
5. ROUTES OF EXPOSURE
5.1 Oral
Foodborne botulism
This is caused by ingestion of food contaminated by a preformed neurotoxin of the bacterium
Clostridium botulinum. Home-preserved foods containing fish, vegetables, or potatoes are often
involved in outbreaks of botulism. High acid content foods are rarely involved. C. botulinum spores
are heat-resistant but the toxin is heat-labile. Boiling food to ensure thorough heating of the interior
should destroy the toxin (Cherington, 1998).
Infant botulism
This is a result of colonization of the intestinal tract after ingestion of spores of C. botulinum. The
infant intestinal tract often lacks both the protective bacterial flora and the clostridium-inhibiting bile
acids found in normal adult intestinal tract. Honey was found to be the vehicle of the spores in 26
cases (Arnon, 1992). Most cases occur before the age of 6 months. Microbiologic surveys of honey
products have reported the presence of clostridial spores in up to 25 % of products. For this reason,
honey should not be given to children during the first year of life (Cherington, 1998; Hatheway,
1995; Shapiro et al, 1998).
In most cases, the responsible food could not be identified. One adult appeared to develop botulism
47 days after exposure to a food that caused botulism in four other family members (Hatheway,
1995).
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5.2 Inhalation
Studies in monkeys indicate that, if aerosolised, botulinum toxin also can be absorbed through the
lung (Shapiro et al, 1998).
Three cases of botulism in laboratory workers have been ascribed to inhalation of the toxin
(Cherington, 1998).
Recent concern about the use of C. botulinum neurotoxin aerosol in a terrorist attack has drawn
attention to the potential risk to public health and the need for preventive measures to be developed
(Steffen et al, 1997). This prompted the development of a heptavalent (type A-G) equine botulinum
immune globulin (BIG) containing purified F(ab)
2
by the United States army (Middlebrook & Brown,
1995).
5.3 Dermal
Neither the spores nor the neurotoxins are able to penetrate intact skin. However damaged skin
may be affected (Slovis & Jones 1998)

5.4 Eye
No data available.

5.5 Parenteral
Wound botulism
The first case of wound botulism was published in 1951. The case occurred in 1943 and involved
an adolescent girl who had sustained an open fracture of her left leg and right ankle following a fall
from a building (Mechem & Walter, 1994). At the time of that review, a total of 40 cases had been
reported in the English-language literature.
Several cases have been reported following intramuscular administration of the toxin for therapeutic
purposes (Cherington, 1998; Bhatia et al 1999).
5.6 Others
No information available.
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6. KINETICS
6.1 Absorption by route of exposure
No data available

6.2 Distribution by routes of exposure
Botulinum toxins are absorbed from the intestinal tract or the infected wound site and are carried via
the lymphatic system, and from the intestinal tract by the bloodstream to the neuromuscular
endings. Toxin types differ in their affinity for nerve tissue, with type A having the greatest affinity
(Midura, 1996). The toxin must enter the nerve ending to exert its effect. Binding of toxin to both
peripheral and central nerves is selective and saturable. Pharmacologic and morphologic data
suggest that internalisation is via a receptor-mediated endocytotic/lysosomal vesicle pathway. The
process is independent of Ca
++
concentration, is partially dependent on nerve stimulation, and is
energy dependent (Brin, 1997).

6.3 Biological half-life by routes of exposure
No data available.

6.4 Metabolism
No data available.

6.5 Elimination and excretion
No data available.

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7. TOXINOLOGY

7.1 Mode of action
Botulinum neurotoxin reaches nerve terminals at the neuromuscular junction, where it binds to the
neuronal membrane, moves into the cytoplasm of the axon terminal, and acts to block excitatory
synaptic transmission, leading to flaccid paralysis (Halpern & Neale, 1995). There are three steps
involved in toxin mediated paralysis: 1) internalisation 2) disulphide reduction and translocation 3)
inhibition of the neurotransmitter release (Brin, 1997). The toxin must enter the nerve ending to
exert its effect. Binding of toxin to both peripheral and central nerves is selective and saturable. The
C-terminal half of the heavy chain determines cholinergic specificity and is responsible for binding,
while the light chain is the intracellular toxic moiety. If the disulphide bond that links the two chains
is broken before the toxin is internalised by the cell, the light chain cannot enter and there is virtually
complete loss of toxicity (Brin, 1997).

The toxin blocks the release of acetylcholine but not its synthesis or storage. Botulinum toxin is a
zinc endopeptidase specific for protein components of the neuroexocytosis apparatus. It cleaves
synaptobrevin, a membrane protein of synaptic vesicles. The types A, C and E act on proteins of
the presynaptic membrane. Types A and E cleave SNAP-25 while serotype C cleaves syntaxin
(Schiavo et al, 1995; Montecucco et al, 1996).

7.2 Toxicity
7.2.1 Human data

7.2.1.1 Adults

Comprehensive reviews of the epidemiology, clinical features and management
principles have been published in recent years (Hauschild, 1992; Hatheway, 1995;
Cherington, 1998; Shapiro et al, 1998; CDC, 1998).

Foodborne botulism
New food items were involved in outbreaks like home-made sauce, baked potatoes
sealed in aluminium foil, cheese sauce, sauted onions held under a layer of butter,
garlic in oil, and traditionally prepared salted or fermented fish. The use of modern
plastic containers introduced a new risk factor in the ingestion of traditional food in
the arctic regions (Hauschild, 1992; Proulx et al, 1997).
A recent comparison of the severity of botulism by toxin type found that
endotracheal intubation was required for 67 % of type A patients, 52 % of type B,
and 39 % of type E (Woodruff et al, 1992). Severity scores for classification of
botulism have been proposed (Roblot et al, 1994).
Wound botulism
This has also been reviewed from the published literature and from a cluster of
cases related to the use of black tar heroin (Burningham et al, 1994; Crawford,
1994; Maselli et al, 1997; Anderson et al, 1997).
This has also been described with greater frequency in recent years (Hatheway,
1995; Shapiro et al, 1998; Cherington, 1998). It is generally associated with
abdominal surgery, gastro-intestinal diseases or asymptomatic exposure to
contaminated food. It may be hypothesised that the use of anti H
2
histamine
medication in these patients may favour the intestinal colonization by C. botulinum
16
since the toxin complex is stable under acidic conditions but dissociates under
slightly alkaline conditions.
7.2.1.2 Children
Infant botulism has also been the subject of comprehensive review (Midura, 1996;
Glatman-Freedman, 1996; Pickett et al, 1976; Long, 1984; Arnon, 1992;
Wiggington & Thill, 1983). The ingestion of honey has been implicated in many
cases but the source of contamination is frequently unknown. It occurs among
children less than one year of age and mostly in the first six months of life. It has a
wide spectrum of severity. Some infants manifest with only mild symptoms and may
go unrecognised while other cases present as sudden infant death syndrome.
Hospitalisation averages approximately five weeks, but may last up to six months.
Infant botulism has been reported from countries all over the world except Africa.
Most cases were reported in the United States. The toxin types involved in these
cases were A and B in approximately the same proportion.
7.2.2 Relevant animal data
The parenteral median LD
50
of botulinum toxin in monkeys and mice is 0.4ng/kg (Gill
1982).
Botulism also occurs in animals. The clinical features are essentially the same as in
humans The toxin involved in these cases was either C or D (Hatheway, 1995). A detailed
review of the subject has been published (Smith & Sugiyama, 1988).
Animal models were used to evaluate the efficacy of the antitoxins (Middlebrook & Brown,
1995). Guinea pigs were given 20 IU human botulinum immune globulin per kilogram
either 4 hours before or 4 to 8 hours after an oral challenge of type A toxin, and all
survived with no clinical signs.
Guinea pigs treated with 1 IU/kg trivalent botulism antitoxin were completely protected
from subcutaneous toxin challenge, although protection decreased when antibody was
given post challenge.
Supportive care improves the efficacy of botulinum antibody therapy in monkeys.
Infant botulism
Using a mouse model system of intestinal colonization it was demonstrated that the
intestinal microflora of adult animals ordinarily prevents colonisation of the intestines by C.
botulinum (Moberg & Sugiyama, 1979). The infective dose of spores for infant mice was
much smaller than that of their antibiotic-treated adult counterparts; the 50 % infective
dose for normal infant mice was only 700 spores (Midura, 1996). In one experiment
10 spores were sufficient to infect an infant mouse (Sugiyama & Mills, 1978).

7.2.3 Relevant in vitro data

Detailed reviews of the chemistry, pharmacology, toxicity, immunology and mechanism of
action of botulinum neurotoxins have been published in recent years (Halpern & Neale,
1995; Middlebrook & Brown, 1995; Schiavo et al, 1995; Montecucco et al, 1996; Brin,
1997; Coffield et al, 1997). The nucleotide sequence for all seven toxin types has been
elucidated (Shapiro et al, 1998).

17
7.3 Carcinogenicity
No data available.

7.4 Teratogenicity
There is no evidence to date that the fetus is at risk of neonatal botulism when the mother is
affected by botulism (Cherington, 1998). There are a few case reports in the literature where the
mother acquired botulism during pregnancy. In no case there was there evidence of transport of the
toxin across the placental barrier.

7.5 Mutagenicity
No data available.

7.6 Interactions
Aminoglycoside antibiotics potentiate the neuromuscular blockade induced by botulinum toxins both
in the human experience of infant botulism and the mouse model (Wang, 1984). Cathartic agents
containing magnesium should be avoided because of the theoretical concern that increased
magnesium levels may enhance the action of botulinum toxin (Shapiro et al, 1998).

8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan
8.1.1 Sampling and specimen collection
Specimens of serum, faeces, vomitus and gastric contents, together with implicated foods
should be collected for testing for toxin and the presence of C. botulinum (Shapiro et al,
1998).

In wound botulism wound exudate, debrided tissue, or a swab sample should be obtained
for anaerobic culture. Serum should also be collected for serum toxin assay and a stool
specimen should be collected to exclude foodborne botulism. In infant botulism, stools
should be collected for culture and toxin identification.

Serum should be collected before antitoxin is given, otherwise there may be a false
negative result. If possible at least 3ml of serum should be collected, although as little as
0.5ml may be sufficient. A larger volume, ideally 10-15ml, will allow specific identification
of the botulinum toxin involved and repeat testing if necessary (CDC, 1998)

8.1.1.1 Toxicological analyses

The mouse innoculation test is still the most reliable method. The type of toxin,
particularly A, B, and E can be detected by injecting the specific antitoxin in
combination with the patients serum into the mouse (Griffin et al, 1997).

8.1.1.2 Biomedical analyses

The differential diagnosis of botulism with other neurological diseases may require
rapid repetitive electromyography, lumbar puncture, edrophonium chloride testing,
18
magnetic resonance imaging or computed tomography of the brain (Shapiro et al,
1998; Cherington, 1998).

8.1.2 Storage of laboratory samples and specimens


All specimens except those from wounds should be refrigerated, preferably not
frozen, and examined as soon as possible. Wound specimens should be placed in
anaerobic transport devices and sent to the laboratory without refrigeration (CDC,
1998).

Food should be left in its original container if possible or placed in a labelled,
unbreakable, sterile container.

8.1.3 Transport of laboratory samples and specimens


Samples should be conveyed to the laboratory as quickly as possible. The samples
should be packed in sterile, leakproof containers. If they have to be sent a long
distance then the samples should be placed in insulated shipping containers with
refrigerant. If a delay of several days is likely then serum and stool samples should
be frozen and packed in dry ice. Packaging should be adequately labelled to
indicate that the contents are a biological hazard (CDC, 1998).
19

8.2 Biomedical investigations and their interpretation
8.2.1 Biochemical analysis

8.2.1.1 Other fluids

CSF is normally clear, although a slightly elevated protein level is sometimes seen
(Hughes et al, 1981).

8.4 Other biomedical (diagnostic) investigations and their interpretation
Electromyography, including single fibre electromyography (SFEMG) may be useful in differential
diagnostics.

9. CLINICAL EFFECTS

9.1 Acute poisoning
9.1.1 Ingestion
Foodborne botulism
The initial symptoms may occur 18 to 36 hours post ingestion. They may be gastro-
intestinal especially in type E and include nausea, vomiting, abdominal cramps or
diarrhoea. Constipation will predominate after the onset of neurological symptoms. The
initial symptoms are dry mouth, blurring of vision and diplopia. These may be followed by
ptosis, ophthalmoplegia, dysarthria, and dysphagia. These abnormalities of the cranial
nerve are followed by a symmetrical descending pattern of weakness and paralysis. After
the cranial nerves, the toxin affects the upper extremities, the respiratory muscles and,
finally the lower extremities. If patients show signs of progression, they should be
closelymonitored for respiratory difficulties.
In severe cases, respiratory muscle paralysis may lead to ventilatory failure and death
unless supportive care is provided (Shapiro et al, 1998). Ventilatory support may be
required for long periods of time in severe cases (2 to 8 weeks). This increases the risk of
medical complications. The recovery of autonomic function takes longer than that of
neuromuscular transmission. Fatality rates are higher for older patients (greater than 60
years) and those who were index patients (the first patient in an outbreak), but antitoxin is
effective in preventing progression of disease and in shortening the duration of ventilatory
failure (Tacket, 1984).
Infant botulism
Infant botulism occurs in children of less than one year of age and mostly during the first 6
months of life. The clinical symptoms vary greatly from case to case. Constipation is
frequently the first symptom, defined as 3 or more days without defecation. Progressive
weakness and poor feeding follow after a few weeks. The weakness is symmetrical and
descending as in foodborne botulism. It evolves over hours to several days. Other
symptoms include lethargy, difficulty in sucking and swallowing, weak cry, hypotonia,
pooled oral secretions and loss of head control.
Neurologic symptoms may include ptosis, ophthalmoplegia, weak gag reflex, dilated and
sluggish pupils, dry mouth and neurogenic bladder.
20
The severity of the clinical picture varies from a mild intoxication to a fatal illness.
However, prognosis is good with proper supportive treatment.
The clinical features of adult infectious botulism are similar to those of foodborne botulism
except for the initial gastrointestinal symptomatology. The interval between bowel surgery
or food exposure and the onset of clinical features may be one or more months. The
clinical severity in reported cases has been quite variable.
9.1.2 Inhalation
Studies in monkeys indicate that, if aerosolised, botulinum toxin also can be absorbed
through the lung (Shapiro et al, 1998).
9.1.3 Skin exposure
Neither C. botulinum spores nor its neurotoxins can be absorbed through intact skin,
however damaged skin may be affected (Slovis & Jones 1998).
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
Wound botulism
Out of 40 published cases in the literature (Mechem & Walter, 1994) 78 % had a clear
history of wounds, including abrasions, avulsions, lacerations, puncture wounds and
abscesses. In other patients, the site of inoculation was obscure.

9.2 Chronic poisoning
9.2.1 Ingestion

Strictly speaking there is no such thing as chronic poisoning by botulism. In the cases of
adult infectious botulism and infant botulism, the clinical picture may last several days or
weeks. However, it is probably caused by a single exposure.

9.2.2 Inhalation

No data available.

9.2.3 Skin exposure

No data available.

9.2.4 Eye contact

No data available.

21
9.2.5 Parenteral exposure

No data available.

9.3 Course, prognosis, cause of death
Foodborne botulism
The symmetrical descending paralysis, when it occurs, usually appears 18 to 36 hours after
exposure and generally lasts for 2 to 8 weeks. However, in severe cases, ventilatory support may
be required for up to 7 months (Shapiro et al, 1998).

The prognosis is dependent on the quality of the supportive treatment. If adequate ventilation is
maintained, the prognosis is good. If, however, ventilatory support is required for a long period of
time (weeks to months) risks of medical complications (respiratory infections, ARDS) increase
significantly. The improvement of critical care in recent years has reduced mortality from 50% to 9%
(Cherington, 1998).

The cause of death in the first days following ingestion is respiratory failure due to a lack of
adequate ventilatory support. In cases requiring long term ventilatory support, death is generally
caused by medical complications.

Infant botulism
The course of the disease is extremely variable. Some are the fulminant type and difficult to
differentiate from the Sudden Infant Death Syndrome (Midura, 1996). When the onset of illness is
sufficiently gradual to permit hospitalisation, the prognosis is excellent.

Wound botulism
The prognosis for patients with wound botulism is favourable, assuming adequate ventilatory
support is maintained (Mechem & Walter, 1994). The case-fatality rate for wound botulism is
approximately 15 % (Shapiro et al, 1998).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Autonomic nervous system instability may induce tachycardia and hypertension.
Orthostatic hypotension may also occur (Cherington 1998, Shapiro et al 1998).
9.4.2 Respiratory
Respiratory depression is caused by respiratory muscle paralysis. It may lead to
ventilatory failure and death.
9.4.3 Neurological
9.4.3.1 CNS
Paralysis of cranial nerves causes blurred vision, diplopia, dysphonia, dysarthria
and dysphagia.
22
9.4.3.2 Peripheral nervous system
Following the paralysis of the cranial nerves, a symmetrical descending paralysis
will occur. It will affect the upper extremities, then the respiratory muscles, and,
finally, the lower extremities in a proximal to distal manner.
9.4.3.3 Autonomic nervous system
Botulinum toxin causes a blockade of the autonomic cholinergic junctions resulting
in dry mouth, blurred vision, orthostatic hypotension, constipation and urinary
retention.
9.4.3.4 Skeletal and smooth muscle
Therapeutic use of botulinum toxin by direct injection of the drug produces a variety
of histological changes (Montecucco et al, 1996). However, this has not been
studied in cases of poisoning.
A case of gallbladder dysfunction induced by botulin A toxin has been described
(Schnider P et al, 1993) as well as necrotising fasciitis as complication of botulinum
toxin treatment (Latimer et al, 1998).
9.4.4 Gastrointestinal
Gastrointestinal symptoms may be observed 18 to 36 hours after ingestion in foodborne
botulism. They include nausea, vomiting, abdominal cramps, and, occasionally, diarrhoea.
In a later phase, after the onset of neurological symptoms and signs, constipation may
occur. Gastric dilatation and paralytic ileus have been described (Adorjan et al, 1998).
Constipation is also frequently observed in infant botulism.
9.4.5 Hepatic
The liver is not affected by botulinum toxins.
9.4.6 Urinary
9.4.6.1 Renal
No direct effect.
9.4.6.2 Other
Neurogenic bladder may occur in the various forms of
botulism.
9.4.7 Endocrine and reproductive systems
No direct effect.
9.4.8 Dermatological
No direct effect.
23
9.4.9 Eye, ear, nose, throat: local effects
Blurred vision, dysphagia, dry mouth, diplopia, dysarthria, ptosis, extraocular muscle
weakness, reduced gag reflex, tongue weakness, fixed or dilated pupils, nystagmus may
all be observed following the toxin induced blockade of cranial nerves and autonomic
nervous system.
9.4.10 Haematological
No data available.
9.4.11 Immunological
Severe allergic reactions may occur following administration of the equine antitoxin.
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
Respiratory acidosis may occur if the ventilation is not properly supported.
9.4.12.2 Fluid and electrolyte disturbances
No data available.
9.4.12.3 Others
No data available.
9.4.13 Allergic reactions
None with the botulinum toxin but allergic reactions may occur with the administration of
the equine antitoxin.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
Foodborne botulism
Home-canned and home-preserved food, uncured ham or sausages. Traditional food
made with fish or sea-mammals.
Infant botulism
Ingestion of honey has implicated in some cases. Intestinal colonisation in adults has
been associated with bowel surgery and chronic inflammatory disease of the intestine.
24
The therapeutic use of botulinum toxin needs special caution in patients with disturbed
neuro-muscular transmission (myasthenia, Lambert-Eaton syndrome) and in patients
concomitantly treated with aminoglycosides (Borodic, 1998; Wang et al, 1984).
A case report indicates that necrotising fasciitis can be a complication of botulinum toxin
injection (Latimer et al, 1998).

9.5 Other
No data available.

10. MANAGEMENT

10.1 General principles
Supportive treatment, especially adequate mechanical ventilation, is of prime importance in the
management of severe botulism. Surgical debridement and antimicrobial treatment are also
required in wound botulism. Antitoxin administration is the only specific pharmacological treatment
available.

10.2 Life supportive procedures and symptomatic/specific treatment
Adequate mechanical ventilation is required following respiratory muscle paralysis caused by
botulinum toxin. This may be required for a period of weeks or even months, especially in infant
botulism. Special care should be taken in order to prevent secondary infections.

10.3 Decontamination
Foodborne botulism
The efficacy of gastric decontamination in preventing botulism has not been studied. Since the
features of foodborne botulism do not appear for several hours it is unlikely that gastric
decontamination would be useful in an already symptomatic patient. In the case of recent ingestion
(<1 hour) of possibly contaminated food emptying the stomach by induction of vomiting with syrup
of ipecac, or by gastric lavage could be considered. Administer activated charcoal and a cathartic
(such as sorbitol). Cathartic agents containing magnesium salts should be avoided because of the
theoretical concern that increased magnesium levels may enhance the action of botulinum toxin
(Shapiro, 1998).
Wound botulism
Surgical debridement should be performed.

25

10.4 Enhanced elimination
There is no way to increase the elimination of the toxin.

10.5 Antidote/antitoxin treatment
10.5.1 Adults
Foodborne botulism
One vial (7500 international units of type A, 5500 international units of type B and 8500
international units of type E antitoxins) equine antitoxin should be administered by infusion
(Shapiro, 1998). Because of the risk of an allergic reaction to the equine serum, the
patient should be asked about past history of asthma, hay fever or allergic reactions when
in contact with horses.
Epinephrine chlorhydrate solution (1:1000) 1 mL should be available for immediate
administration if required.
Sensitivity test:
An ocular or cutaneous sensitivity test should be performed prior to administration of the
equine antitoxin.
Cutaneous test:
0.1 mL of the antitoxin serum diluted 1:100 in normal saline is administered by
subcutaneous injection. If there is a positive history of allergies, this dose should be
reduced to 0.05 mL of a 1:1000 dilution by subcutaneous injection. The interpretation of
the result is done after 5 to 30 minutes. It is considered positive if a papule with a
hyperemic areola occurs. The size of the papule and of the hyperemic zone give an
indication of the level of sensitivity of the patient and the risk of an adverse effect to the
administration of the antitoxin.
N.B. A negative cutaneous sensitivity test does not entirely exclude the possibility of a
serum reaction.
Except in young children, an ocular test is easier to perform and produces less non-
specific reactions. A drop of antitoxin serum diluted to 1:10 in a solution of normal saline is
instilled in one eye. A control solution containing only normal saline is instilled in the other
eye. Tears and conjunctivitis represent a positive reaction.
Serum reactions to equine antitoxin serums:
Anaphylactic reaction: Immediately administer 0.5 mL of a solution of epinephrine
chlorhydrate 1:1000 SC or IM.
Fever:
This may occur 20 to 60 minutes after the administration of the antitoxin. It is
characterised by shivering, slight dyspnea and fever.
Serum sickness:
This may occur up to 2 weeks after the administration of the antitoxin. The signs and
symptoms are the following: fever, skin rash, oedema, swelling of the glands, articular
pains. Urticarial reaction may respond to the administration of epinephrine. More severe
cases may require the administration of cortisone.
26
Use of the equine antitoxin in a sensitive person.
Desensitisation protocol:
- 0.05 mL of a 1:20 dilution solution SC
- 0.1 mL of a non diluted solution
- 0.2 mL of a non diluted solution SC
- 0.5 mL of a non diluted solution SC
- Administration of the remaining therapeutic doses IM (Canadian Pharmacists
Association, 1999)
Wound botulism
The treatment is similar to foodborne botulism.
Infant botulism
The use of equine antitoxin therapy is not recommended in children (Shapiro et al, 1998).
However, the safety and efficacy of a human-derived antitoxin product (human botulism
immune globulin) is being investigated in California (USA) for use in infants. For
information on the Infant Botulism Prevention Programme contact the California
Department of Health Services at (510) 540-2646 (24 hours).
The antitoxin protocol is the same as in foodborne poisoning. However, additional doses
of antitoxin may be required. Care should be taken since sensitivity to equine serum may
have been developed since the first administration.
10.5.2 Children
The protocol for the administration of the trivalent antitoxin is similar to the one used in
adults.
27
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Wound botulism
A 27 year old heroin user was admitted with a 2 day history of muscle weakness. On examination
he was afebrile and fully responsive but unable to keep his head upright. He deteriorated over the
next few days, developing symmetrical flaccid paresis of the neck muscles, dysphagia, dysarthria,
dry mouth, eyelid ptosis, mydriasis, diplopia, and urinary retention. He was unable to sit
unsupported and had proximal paresis of all limbs with preserved deep tendon reflexes.
This patient usually administered heroin by subcutaneous or intramuscular injection and was noted
to have several skin wounds. Wound botulism was suspected and he was treated with an
intravenous dose of 500mL of trivalent equine botulism antitoxin (Botulism Antitoxin Behring, Chiron
Behring, Germany) followed by 250mL six hours later. He was also given intravenous
benzylpenicillin 20 megaunits daily, and surgical wound debridement was carried out. He developed
respiratory failure and had to be mechanically ventilated for 16 days.
Electrophysiological investigations on day 26 revealed low compound muscle action potentials in
the right arm and leg. Standard needle electromyography of the affected muscles showed brief low-
amplitude irregular potentials. The diagnosis of wound botulism was confirmed in a mouse bioassay
with serum drawn on day 3, just before administration of antitoxin (Jensenius et al, 2000).
Foodborne botulism
Six cases of botulism were described in Hungary. The first incident involved five members of the
same family. The illness was moderately severe in three patients and mild in two patients. One of
the patients had cirrhosis of the liver, and her condition became critical because of the repeated
bleeding from oesophageal varices. A separate case involved a patient with sporadic illness. This
patient developed severe gastric dilatation and paralysis of the bowels causing ileus at the start of
the illness. In both sets of cases the diagnosis was confirmed by toxin tests in addition to the
symptoms and food history. The symptoms regressed slowly, in about three weeks, in all patients.
There were no deaths (Adorjan T et al, 1998).
28
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
C. botulinum produces heat-resistant spores. Some strains will not survive above 80C, but others
can only be destroyed by heating above boiling point. The thermal resistance of spores increases in
foods with a higher pH and a lower salt content (CDC, 1998).
The growth of C. botulinum is inhibited by high temperature, acidification, dehydration, salination,
certain food preservatives e.g. nitrite, ascorbates, polyphosphates, and competing microorganisms
such as Lactobacillus spp (CDC, 1998). Nitrite and nitrate food preservatives have their own
inherent problems (WHO working group, 1977).
Botulinum toxin is heat labile and can be inactivated by heating to 80C (CDC, 1998).
The prevention of foodborne botulism is achieved by processing food in such a way as to kill
spores, and/or inhibit bacterial growth, and/or denature preformed toxin. Since many cases of
botulism are associated with home-preserved food, public education about the need for adequate
heating, appropriate storage etc is important.
Since honey has been identified as a food source of infant botulism this food should not be given to
infants under the age of one year.
29
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14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE ADDRESSES
Author: Albert J Nantel, Scientific Adviser, Centre de Toxicologie du Qubec, August, 1999
Reviewer: Janusz Szajewski, MD
Warsaw Poisons Centre
Telephone +48 22 839 0677
Facsimile +48 22 839 0677
e-mail szajewsk@waw.pdi.net
Reviewed at INTOX 12, Erfurt, Germany, November 2000.
Reviewers: M. Balali-Mood, B. Groszek, W. Temple, N. Langford
Edited by J.Tempowski (IPCS), February 2002 (ipcsintox@who.int)

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